The olfactory system has the difficult task of discriminating between complex odors often made of hundreds of volatile components. The system solves this stringent problem by expressing ~1000 olfactory receptors in the olfactory sensory neurons (OSNs). Each OSN expresses one receptor, and all the OSNs expressing the same receptor target their axons to the same glomeruli. Thus, the glomerulus is a functional unit of activity and all axons within a glomerulus are from OSNs that respond to a subset of volatile components. While this strategy succeeds in forming a glomerular representation of odor quality in the form of a glomerular pattern of activation, this representation is still complex as downstream processing centers must respond to the differential activation of ~2000 glomeruli. The main olfactory bulb is the first circuit responsible for processing the information contained in glomerular activation. Its makeup includes the mitral and tufted cells - projection neurons whose dendrites receive input from a single glomerulus and whose axons transmit the signal to olfactory cortex } and interneurons } granule cells } that make inhibitory dendrodendritic synapses onto mitral cells. This circuit is thought to play an important role in processing odor quality information through its capability of performing nonlinear filtering of the input signal conveyed to the olfactory cortex. In this exploratory research grant application we present exciting preliminary data indicating that the responsiveness of mitral cells to odors changes as mice learn to differentiate between two odors. In the application we propose to refine and validate a technique for awake behaving recording from OB units to test the hypothesis that odor responsiveness of mitral cells (MCs) changes during learning in a go-no go odor discrimination task. PULBLIC HEALTH RELEVANCE: Project Narrative In humans disorders of the sense of smell are encountered in diseases such as Alzheimer's (Doty, 1991;Rawson, 2000), bipolar depression (Hahn et al., 2005) and schizophrenia (Turetsky et al., 2003). Our work is relevant because problems in the modulation of OB activity during learning could underlie some of these pathologies. [unreadable] [unreadable] [unreadable]